Throughout a synthetic organic chemist’s career, reaction planning, execution, and analysis will be repeated countless times. The objective of my thesis research was to expedite this workflow to more efficiently access to novel, complex, and biologically useful molecules and synthetic methods. Since the mid 20th century there have been several significant advances that have fundamentally improved how organic chemists synthesize molecules and develop reactions. Among these developments are the institution of thorough mechanistic analysis, the introduction of structural and conformational analysis of molecules via spectroscopic methods, and the application of chromatographic methods to separate and analyze organic compounds. This thesis outlines our efforts to further accelerate synthetic organic advancement through the development and application of new synthetic planning and reaction screening technologies. The first chapter details our investigation and assessment of the retrosynthetic software, Chematica, a machine-learning program intended to accelerate synthetic planning. This chapter describes our attempts to synthesize three different targets, adhering to Chematica-generated routes. Such efforts allowed us to identify significant weaknesses present in the software, which, once corrected will likely improve the program. Supplementing the computer program’s route with necessary organic expertise, the first stereoselective syntheses of the natural product (–)-dauricine and its enantiomer (+)-dauricine were achieved. The second chapter focuses on our attempts to expedite reaction discovery and optimization. We introduce a novel high throughput photocapture platform that allows ~2,000 organic reactions to be screened in <2.5 hours, a substantial improvement from the 120+ hours that would be required using a conventional LC-MS method. This platform was applied to the discover a novel photoredox reaction transforming acyl azoliums to ketones via an intermolecular radical-radical coupling reaction. Finally, the third chapter briefly outlines our investigation into the compatibility between our diazirine photocapture platform and 110 different small organic molecules presenting common functional groups. This work outlines general guidelines that will guide future applications of this high-throughput platform in reaction discovery and optimization.

Creator

• Bayly, Alison

DOI

• https://doi.org/10.21985/n2-q63w-4w39

Subject

• Organic chemistry

Language

• en

Alternate Identifier

• http://dissertations.umi.com/northwestern:15017
• etdadmin_upload_719809

Keyword

• High-Throughput Screening
• Photocapture
• Retrosynthetic Planning

Date created

• 2020-01-01

Resource type

• Dissertation

Rights statement

• In Copyright